Osteopenia Is Commonly Present in Prepubertal Children with Severe Hb E/βthalassemia Despite Adequate Transfusion and Iron Chelation Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3830-3830 ◽  
Author(s):  
Vip Viprakasit ◽  
Pairunya Sawathiparnich ◽  
Tuangrat Sangpraypanm ◽  
Linda Weerakulwattana ◽  
Pornpimol Kiattisakthavee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Free T4 ◽  
Hb E ◽  
Severe Group ◽  
Group A ◽  
Group B ◽  
Marrow Expansion

Abstract Objectives: Previous studies showed that low bone mineral density (BMD) is highly prevalent in Hb E/βthalassemia, who received occasional transfusion. Concerning the clinical heterogeneity of this syndrome, we determine whether adequate transfusion and chelation therapy in severe cases with Hb E/β0 thalassemia could ameliorate this complication. Methods: 50 pre-pubertal patients, age from 8–13, were recruited after informed consent. 26 were classified as severe group using Thalassemia International Federation (TIF) criteria, while 24 were mild. In severe patients, each received transfusion every 3 weeks (12–15 ml/kg) to keep their pre-transfusion Hb at 10 g/dL and they received iron chelation either by deferioxamine (20–40 mg/kg/d) or deferaxirox (25–30 mg/kg/d). Demographic data and history of chelation therapy were recorded. Serum free T4, TSH, PTH, cortisol, 25-OH Vit D, osteocalcin, alkaline phosphatase, serum ferritin (SF), Ca and P were determined. We measured the BMD of lumbar spines (L2-L4) and total body using DEXA (Lunar, Prodigy) and adjusted for height-age (HA) and bone age (BA). WHO criteria for BMD was Z-score −1 to −2.5 = osteopenia and < −2.5 = osteoporosis. Results: They were compound heterozygotes of Hb E with either codon 41/41 (50.6%), codon 17 (19%), IVS2#654 (14%), IVS1#1 (4%), IVS1#5 (3%) and codon 71/72 (2%) mutations. In severe group, 15 cases had poor compliance for chelation therapy (group A) (average SF; 6027 ± 2564 ng/ml) while 11 cases had good compliance (group B) (average SF; 2374.3 ± 189 ng/ml) and the ferritin level in mild group (group C) were 197 ± 89.4 ng/ml. There were no statistical significances among these three groups regarding baseline Hb, age and sex-distribution, weight, height and their corrected Z-scores for the standard of Thai children. Only the onset of anemia was significant lower in group C (5.4 ±1.8 yrs) compared to 2.12 ± 1.35 and 2.24 ± 2 yrs in group A and B respectively. All had normal free T4, TSH, PTH, Ca and P. As expected, 7 cases (78%) of group A with marked iron overload had osteopenia while one (7%) had osteoporosis. A strong invert correlation between BMD and serum ferritin in this group was observed. To our surprise, 6 out of 11 (54%) in group B and 14 out of 24 (58%) in group C also had osteopenia. However, there was no correlation between BMD and baseline Hb, ferritin and other clinical parameters in the group B and C. Conclusion: Low BMD in thalassemia might be resulted from ineffective erythropoiesis, bone marrow expansion and iron deposition in the bone marrow. In severe Hb E/βthalassemia, despite adequate transfusion, osteopenia and osteoporosis remain highly prevalent especially when iron overload is a co-factor. However, detecting this complication in a “so-call’ milder group was surprising since this group of patients was less anemia and rarely required blood transfusion. These suggest that several factors beside anemia and bone marrow expansion might play roles on developing this complication. Moreover, the current standard transfusion and chelation protocol might not be preventable our patients from bone complications and they were at a greater risk of fracture in adulthood. It will be of interest to investigate whether calcium and Vit D supplement with or without osteoclast inhibitors could prevent osteopenia in this highly common hereditary anemia.

Multidisciplinary Evaluation Improves Efficacy and Safety of Iron Chelation Therapy with Deferasirox in MDS Elderly Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4558-4558
Author(s):  
Lisette Del Corso ◽  
Elisa Molinari ◽  
Andrea Bellodi ◽  
Riccardo Ghio ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Group A ◽  
Group B

Abstract BACKGROUND: Iron overload from chronic transfusion therapy can be extremely toxic and most patients (pts) do not receive adequate iron chelation therapy (ICT) despite evidence of transfusional iron overload (IOL). Deferasirox (DFX) is the principal option currently available for ICT in the management of IOL due to transfusion dependent anemia, such as in MDS pts. The most common adverse events (AEs) are gastrointestinal disorders, skin rash, elevations in liver enzymes levels and non-progressive transient increases in serum creatinine also in MDS pts, most of whom are elderly with significant comorbidities and side effects of other concomitant therapies. In order to achieve effective ICT with minimal toxicity in individual pts, regular monitoring to assess IOL and adverse effects of DFX treatment is essential. METHODS: The safety and efficacy of DFX were examined in a retrospective multicenter observational study of transfusion-dependent (TD) MDS pts with International Prognostic Scoring System (IPSS) low-or Int-1-risk. We included all pts treated with DFX up to 12 months, divided into two groups; the first one (group A) not under a multidisciplinary assessment, including pts not adequately treated, in terms of dosing and discontinuation of ICT and the second one (group B) with pts under multidisciplinary control. The DFX starting dosing was 10 mg/kg/die in all pts. The aim of our retrospective analysis was to assess the effectiveness of ICT in relation of dosing and right management of AEs. RESULT: We evaluated 45 MDS pts (12F/33M); 27 belonging to the group A and 18 to group B. The age was 74.2±8.8 and 77.3±4.8 respectively. The ECOG 0-1 was 85,1% in group A and 88,9% in group B. The transfusion episodes prior starting DFX were22.1±12.1 and 24.5±35.4 in the first and in the second group, respectively. The serum ferritin level at baseline was respectively 1285.1±489.6 ng/mL and 1452.6±748.1 ng/mL. The mean serum ferritin level increased from 1285.1+489.6 ng/mL to 1412.1+842.8 ng/mL in group A while decreased from 1452.6+748.1 ng/mL to 1166.1+ 723.4 ng/mL in group B. The rate of inadequate therapy, in terms of dosing and/or discontinuation ICT, was 85% in group A compared to 60% in group B (p= 0.086).The rate of severe SAE observed in all pts was 10%.The most common AEs were diarrhea, nausea, upper abdominal pain, serum creatinine increase. The positive hematological response rate was observed in 15% of all pts. CONCLUSIONS: The study showed that group B obtained advantage in terms of efficacy and toxicity. The difference between the two groups derived from the ability to manage comorbidities, concomitant therapies and AEs, in particular the rise in serum creatinine, the most common cause DFX discontinuation or dosing reduction. In this setting, the most important specialist was the nephrologist. In our multidisciplinary group experts in management of ICT were hematologist, internist, immune-hematologist and nephrologist. We shared how we monitored kidney function and managed a possible nephrotoxicity (table.2), in order to ensure DFX efficacy. Positive hematological responses were observed, and a subset of pts achieved transfusion independence. The timing of future multidisciplinary evaluation is set on 24 and 36 months, time in which we expect the best response to DFX therapy. Table 1. Ferritin trend group A (n27) group B (n18) Ferritin N mean±SD Median (range) N mean±SD Median (range) Baseline 27 1285.1±489.6 1134 (388-2099) 18 1452.6±748.1 1515 (160-3018) 3 months 22 1451.5±720.5 1247.5 (529-2791) 13 1312.7±909.8 1064 (521-3859) 6 months 23 1850.5±1079.1 1419 (374-4185) 11 1168.4±648.4 1300 (160-2409) 12 months 17 1412.1±842.8 1372 (111-3127) 9 1166.1±723.4 930 (277-2536) Table 2. Management of renal changes during therapy with DFX Creatinine and urine examination:1) in two successive determinations prior to initiation of therapy, then every month 2) in pts with other risk factors for kidney disease, every week for 1 month after start of DFX or dose increase and, subsequently, every month Changes in creatinine:1) increased by 33% in two successive determinations: reduce DFX dose of 5 mg/kg 2) progressive increase of creatinine: interrupt DFX and then re-challenge it at a lower dose with gradual increase if the clinical benefits outweigh the risks Disclosures No relevant conflicts of interest to declare.

Deferasirox Improves Liver Pathology In β-Thalassemia Patients with Transfusional Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4274-4274 ◽  
Author(s):  
Yves Deugnier ◽  
Bruno Turlin ◽  
Victor Dong ◽  
Vanessa Giannone ◽  
Yiyun Zhang ◽  
...  
Keyword(s):  
Iron Overload ◽  
Success Rate ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Total Iron ◽  
Iron Chelation Therapy ◽  
Liver Pathology ◽  
Liver Iron ◽  
Group A ◽  
Group B

Abstract Abstract 4274 Background: While iron overload is known to cause hepatic toxicity, the effect of iron chelation therapy on liver pathology is not well understood. Data evaluating liver fibrosis during iron chelation therapy are limited to small studies (eg, Wu SF et al. Hemoglobin 2006 [n=17], Berdoukas V et al. Hematol J 2005 [n=49], Wanless IR et al. Blood 2002 [n=56]). In order to address such effects in a more robust patient population, we assessed liver biopsy samples from β-thalassemia patients enrolled in two large clinical studies (Porter J et al. Blood 2005, Cappellini MD et al. Blood 2006) that evaluated the effects of deferasirox on iron burden for up to 5 years. Methods: Patients with β-thalassemia and transfusional hemosiderosis receiving ≥8 blood transfusions/year, with liver biopsy assessment (defined as having either liver iron concentration [LIC], Ishak grading or Ishak staging assessment), after at least 3 years of deferasirox treatment, were included. Deferasirox dose was 5–40 mg/kg/day based upon level of iron overload (Study 107, patients randomized to deferoxamine [DFO] or deferasirox for the first year; Study 108, patients received deferasirox only). Treatment response success was defined according to baseline (start of deferasirox dosing) and end-of-study (EOS) LIC measurements (Table). Histological total iron score (TIS) was derived from the iron load observed in hepatocytes (hepatocytic iron score [HIS] range, 0–12), sinusoidal cells (sinusoidal iron score [SIS] range, 0–4) and main structures of the portal tracts (portal iron score [PIS]). A heterogeneity factor (H = 1, 2 or 3) was then applied, based on the overall appearance of the tissue, to provide TIS, calculated as (HIS + SIS + PIS) × (H/3) [range 0–60]. Hepatocytic to total liver iron ratio was calculated as HIS/(HIS + SIS + PIS) (Deugnier Y et al. Gastroenterol 1992). Fibrosis staging was performed according to Ishak scale from 0 (no fibrosis) to 6 (cirrhosis, probable or definite). Liver inflammation was assessed according to the Ishak necroinflammatory grading system with an overall scoring range from 0–18 (Ishak K et al. J Hepatology 1995). Results: Of 770 patients enrolled in the deferasirox studies, 219 with histological biopsy data at baseline and at the end of at least 3 years of treatment with deferasirox were eligible for analyses. Mean LIC was 15.7 ± 9.9 mg Fe/g dw and median serum ferritin was 2069 ng/mL (range 273–11698) at the start of deferasirox treatment. After at least 3 years of treatment, overall LIC success response rate was 63.8% (n=134), and mean LIC decreased by 5.5 ± 10.6 to 10.1 ± 8.2 mg Fe/g dw. Mean absolute change in TIS and liver iron ratio were -8.2 ± 13.3 and -2.1 ± 27.3, respectively. The range of Ishak necroinflammatory scores at baseline was 0–8 with a mean of 2.0 (2.2 in patients who met success rate criteria [Group A], 1.6 in patients who did not meet the success rate criteria [Group B]). At EOS the necroinflammatory score improved to a mean of 0.8 overall, and in both subgroups, with a mean relative change of -66% (69% in Group A and -61% in Group B). Overall 83.3% (n=175) [85.8% (n=115) in Group A, 78.9% (n=60) in Group B] of patients experienced either stabilization or improvement in their Ishak fibrosis score. Ishak staging remained stable (change of -1, 0 or +1) in 55.7% (n=122) of patients. Fifty-nine patients (26.9%) had an improvement in Ishak grading by a score of ≥2. Similar improvements were observed between Group A (26.1%, n=35) and Group B (30.3%, n=23). Conclusions: This is the first study to assess the effect of iron chelation therapy on liver pathology in a large cohort of iron-overloaded patients with β-thalassemia. In addition to reducing total iron burden, deferasirox led to an improvement in pathological markers of iron overload-induced liver damage in the majority of patients; 83.3% showed stabilization or improvement in Ishak fibrosis staging as well as an overall improvement in necroinflammatory score. These effects were similar in both patients who met the LIC success rate criteria and those who did not, suggesting that the observed effects may be at least partly independent of the drug's chelation effect. These findings are important as stabilization or regression of hepatic fibrosis in the face of chronic insult may prevent progressive liver disease. Disclosures: Deugnier: Novartis: Honoraria. Dong:Novartis: Employment. Giannone:Novartis: Employment. Zhang:Novartis: Employment. Griffel:Novartis: Employment. Brissot:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Iron Overload and Haematopoiesis in MDS: Does Blood Transfusion Promote Progression to AML?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2685-2685 ◽  
Author(s):  
Lap Shu Alan Chan ◽  
Rena Buckstein ◽  
Marciano D. Reis ◽  
Alden Chesney ◽  
Adam Lam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Bone Marrow Cells ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Ferritin Concentration

Abstract Introduction: The biology of myelodysplastic syndrome (MDS) is poorly understood, and treatment options are limited. Thus, most MDS patients require chronic red blood cell transfusion, and many develop secondary iron overload. Although the pathophysiological consequences of iron overload to the heart, liver, and endocrine organs have been well characterized, its effects on haematopoiesis have not been studied. However, it has been observed that chelation therapy in iron-overloaded MDS patients may result in reduction of transfusion requirements, and recent studies have suggested a correlation between the use of iron chelation therapy and improvement in leukaemia-free survival in MDS. At the cellular level, iron toxicity is mediated in large part via the generation of reactive oxygen species (ROS). It has been shown in animal models that accumulation of ROS leads to senescence of haematopoietic stem cells, and that ROS cause DNA damage and promote the development of malignancy. These effects of ROS may be particularly important in MDS, in which haematopoiesis is already severely compromised and genetic instability is a striking feature. Hypothesis: We hypothesize that iron overload secondary to transfusion leads to increased levels of intracellular ROS in early haematopoeitic cells in MDS. The increase in intracellular ROS in MDS would be predicted to lead further impairment of haematopoiesis via stem cell exhaustion and while promoting accumulation of DNA damage by myelodysplastic stem cells and early progenitors, thus accelerating progression of MDS to acute leukaemia. Results: To test this hypothesis, we examined the relationship between transfusion-related iron overload and ROS content of CD34+ bone marrow cells in MDS. ROS content was measured in CD34+ cells by flow cytometry in bone marrow aspirates from 34 consecutive MDS patients (CMML=4, MDS/MPD=2, RA=4, RARS=3, RCMD=2, RAEB 1=6, RAEB 2=12, RAEB-t/AML=1). The patients represented a wide range of prior transfusion burden (0->300 units PRBC) and serum ferritin levels (11->10000 μg/L). ROS was strongly correlated with serum ferritin concentration for patients with iron overload (serum ferritin >1000 μg/L; n=14, R=0.733, p<0.005). The correlation between ROS and ferritin level was even stronger in the subset of patients with RAEB 1 or RAEB 2 and iron overload (n=11, R=0.838, p<0.005). In contrast, no correlation between ROS and ferritin level was demonstrated for patients with serum ferritin <1000 μg/L (n=20). Importantly, iron chelation therapy was associated with a reduction in CD34+ cell ROS content in one patient. To assess the effect of iron overload on normal stem cell and progenitor function, we established a mouse model of subacute bone marrow iron overload. B6D2F1 mice were loaded with iron dextran by intraperitoneal injection (150mg total iron load over 21 days), and sacrificed three days after the end of iron loading. Iron staining of tissue sections confirmed iron deposition in the bone marrow, liver, and myocardium. The development of splenomegaly was noted in iron-loaded animals. Flow cytometric analysis revealed increased apoptosis of bone marrow cells in iron loaded mice based on annexin V+/7 AAD-staining (6.26±0.96% versus 3.54±0.99% for control mice, paired student’s t-Test p<0.005). However, ROS content in CD117+ progenitors of iron loaded mice was similar to control mice. Thus, subacute iron loading in mice increases apoptosis but does not alter the ROS content of HSCs; we postulate that chronic iron overload is required to achieve this effect. Conclusions: These results establish a relationship between CD34+ cell ROS content and serum ferritin concentration in MDS patients with iron overload, and indicate that iron chelation therapy in this patient population reverses this ROS accumulation. The physiological consequences of this relationship are currently being investigated in this patient set by haematopoietic colony assays and assessment of DNA damage in CD34+ cells. Nonethelesss, these data may have key implications for the deployment of iron chelation therapy in MDS patients, and may explain the association between the use of iron chelation and improved leukaemia-free survival in MDS.

scholarly journals Some aspects of thyroid dysfunction in thalassemia major patients with severe iron overload

2011 ◽  
Vol 51 (2) ◽  
pp. 66
Author(s):  
Cynthia Rindang ◽  
Jose R. L. Batubara ◽  
Pustika Amalia ◽  
Hindra Satari
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Elevated Serum ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Primary Hypothyroidism ◽  
Iron Chelation Therapy ◽  
Free T4 ◽  
Cross Sectional ◽  
Female Ratio

Background Severe iron overload due to recurrent transfusions for chronic anemia and inadequate iron chelation therapy in thalassemia major patients result in various complications, including hypothyroidism. Currently, there has been no data on the prevalence of hypothyroidism in thalassemia major patients at the Thalassemia Centers, Department of Child Health, CiptoMangunkusumo Hospital (DCH CMH).Objective To study the prevalence of primary hypothyroidism in thalassemia major patients in the Thalassemia Center, DCH MCH.Methods We performed a cross-sectional, descriptive study. All thalassemia major subjects aged O􀁬18 years with severe iron overload underwent thyroid functionexamination. Primary hypothyroidism was defined as either normal (compensated) or decreased (decompensated) free T4 (FT4) levels, along with elevated sensitive thyroid􀁬stimulatinghonnone (TSH)levels. Results 179 subjects enrolled this study Mth male: female ratio of 1: 1.6. The prevalence of primary hypothyroidism in thalassemia majorpatients Mth severe iron overloadws26.8% (48/179). Of those 48,45 had compensated hypothyroidism and 3 had decompensated hypothyroidism, 25.1% and 1.7% of the total subjects, respectively. Compensated hypothyroidism was observed in 17 subjects aged ≤1O years and in 28 subjects aged> 10 years. All 3 decompensated hypothyroidism cases were> 10 years of age. No relationship was found between the occurrence of primary hypothyroidism and mean pre-tr811sfusion Hb levels (P=0.481, OR 1.30; 95% CI 0.63 to 2.68), elevated serum ferritin levels (P=0.74, OR 0.89; 95% CI 0.46 to 1.75), and compliance to iron chelation therapy (P=0.570, OR 0.76; 95% CI 035 to 1.65). Based on multivariate analysis, only age of <10 year-old (P=O.029, OR 0.469; 95% CI 0.23 to 0.93) was significantly associated Mth primary hypJthyroidism. Further analysis using receiver operator curve (ROC) technique found that age of 8.5 year-old was the cutoff value to predict the risk of hypothyroidism. Conclusion The prevalence of primary hypothyroidism in our study is high. The occurrence of hypothyroidism is associated with age.

Cardiac Iron Overload Assessed by T2* Magnetic Resonance (CMR) In Thalassemia Major Patients Treated with Different Iron Chelators

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4275-4275
Author(s):  
Elena Cassinerio ◽  
Alberto Roghi ◽  
Patrizia Pedrotti ◽  
Francesca Brevi ◽  
Laura Zanaboni ◽  
...  
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelators ◽  
Iron Chelation Therapy ◽  
Myocardial Iron ◽  
Cardiac Siderosis ◽  
Group A ◽  
Group B ◽  
Group D

Abstract Abstract 4275 Introduction. Although iron chelation therapy has markedly improved the survival, heart failure due to myocardial iron overload still remains the leading cause of morbidity and mortality in adult thalassemia major (TM) patients. T2* cardiovascular magnetic resonance (CMR) is a non invasive technique that provides rapid and direct assessment of myocardial iron content and its usefulness in monitoring iron chelation has been proved (Wood et al, Circulation 2009). AIM OF THE STUDY. To evaluate the efficacy of different iron-chelation therapies on removal of cardiac iron content assessed by CMR in adult TM patients. PATIENTS AND METHODS. Sixty-seven TM patients (27 males/40 women, mean age 35 ± 6 yrs) treated with different iron chelators underwent repeated cardiac CMR to assess myocardial iron load. Myocardial T2* was assessed at baseline (t0), after 6–14 months (t1) (according to clinical conditions and to T2* at baseline), and as second control (t2) after a mean of 32±7 months from baseline. CMR was performed at Cardiology and CMR Department “A. De Gasperis” at Niguarda Ca' Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). Normal cardiac T2* was defined > 20 ms; T2* < 10 ms indicated severe cardiac siderosis and T2* between 10 and 20 ms moderate-to-mild cardiac siderosis. Each patient has to be chelated with the same iron chelation therapy at least for 1 year before the baseline CMR evaluation. Patients were divided based on chelation therapy in 4 groups: group A (n=36, 53.7 %) patients chelated with deferasirox (DFX, mean actual dose 27±7 mg/Kg/die), group B (n=15, 22.4 %) deferoxamine (DFO, actual mean dose 48±9 mg/kg for a median of 6 days/week), group C (n=12, 17,9 %) DFO (mean actual dose 46±7 mg/kg for a median of 4 days/week) plus deferiprone (DFP, mean actual dose 73±7 mg/kg/day) and group D (n=4,6 %) only DFP (mean actual dose 75±0 mg/kg/day). Statistical analysis was performed using a paired Student's t-test. RESULTS. Overall, the pre-transfusional mean hemoglobin (Hb) was 9.7±0.5 g/dl, the median ferritin value was 913 ng/ml (range 229–5934 ng/ml) and the mean iron intake was 0.41±0.12 mg/Kg/day. In the overall population, the baseline myocardial T2* was < 10 ms in 8 patients (11.9 %), between 10 and 20 ms in 22 patients (32.8 %) and ≥ 20 ms in 37 patients (55.2 %). At baseline evaluation, T2* < 10 ms was detected only in 1 patient (1/36: 2.77 %) in group A, in 4 patients (4/15: 26.6 %) in group B and in 3 patients (3/12: 25 %) in group C. In group D all patients showed a myocardial T2* above 20 ms at baseline. Progressive changes in T2* values were observed at t1 and t2 for all the groups. Ten patients (10/36: 27.8 %) in group A, 3 patients (3/15: 20 %) in group B, 3 patients (3/12: 25%) in group C, respectively, moved from an abnormal T2* (< 20 ms) to normal values, in 32±7 months (Table 1). T2* values at t2 improved significantly compared to baseline (p=0.0006) in patients treated with DFX (group A). In patients treated with combination therapy (DFO and DFP), T2* increased more rapidly in those with severe siderosis (T2* < 10 ms) (p=0.006). No significant changes in left ventricular ejection fraction (LVEF) values were observed in all groups of patients: only patients in group A with baseline cardiac T2* between 10 and 20 ms showed a slight improvement in LVEF (p=0.049). No statistically significant reduction in ferritin levels were associated with ameliorating myocardial T2* values. DISCUSSION AND CONCLUSIONS. Our data showed that compliance to chelation therapy at proper doses significantly improve myocardial T2* over 3-year treatment period. Continued treatment with deferasirox significantly increase myocardial T2* over time, showing its efficacy to remove iron from the heart. DFO and DFP combination therapy seems to ameliorate cardiac T2* more rapidly only in patients with T2* < 10 ms at baseline. Disclosures: No relevant conflicts of interest to declare.

Improvement of Cardiac Function and Cardiac Volumes in Patients Treated with Deferasirox

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2159-2159
Author(s):  
Elena Cassinerio ◽  
Alberto Roghi ◽  
Patrizia Pedrotti ◽  
Laura Zanaboni ◽  
Francesca Brevi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Iron Overload ◽  
Conflicts Of Interest ◽  
Iron Chelation ◽  
Myocardial Iron ◽  
Ventricular Volumes ◽  
Cardiac Morbidity ◽  
Cardiac Iron ◽  
Group A ◽  
Group B

Abstract Abstract 2159 INTRODUCTION. The iron chelation therapy in thalassemia major (TM) patients has been demonstrated to reduce cardiac morbidity and mortality. Deferoxamine (DFO) significantly improved survival but its use has several limitations due to reduced compliance. The once-daily oral chelator deferasirox (DFX) has been shown to remove iron from the liver and from the heart, with improved compliance. The efficacy of DFX in removing cardiac iron has been shown and significant improvements in myocardial T2* in patients with b-thalassemia with T2* levels < 20 ms have been demonstrated. The introduction in the clinical practice of the T2* Cardiac Magnetic Resonance (CMR) evaluation permitted a rapid, direct and highly reproducible method to assess myocardial and hepatic iron overload; moreover this technique allows to evaluate cardiac morphology and function. We evaluated the removal of cardiac iron and the cardiac function parameters in TM patients treated with DFX, undergoing CMR,followed at Hereditary Anemia Centre, Department of Internal Medicine in Milan. METHODS. Forthy-one TM patients (22 females, 19 males, mean age 32 ± 6 yrs), treated with DFX, followed in a single centre, underwent a CMR, performed at baseline (T0), after a variable period of exposure to DFX (median: 12 months, range 4–48 months) and then after at least 6 months of treatment (T1) (median 12 months, range 6–19 months). CMR was performed at Cardiology and CMR Department “A. De Gasperis” at Niguarda Ca' Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). The signal intensity of this region was measured for each image with the use of commercial software (CMRtools, Cardiovascular Imaging Solutions, London, UK). All T2* analyses were performed blinded to patient details. Ventricular volumes were analyzed with the same software and stroke volume and ejection fraction calculated from end diastolic and end systolic ventricular volumes. Patients were divided in two groups: group A (28 patients) with baseline T2* values > 20 ms and group B (12 patients) with baseline T2* between 10 and 20 ms. RESULTS. In the overall population, the mean deferasirox dose was 26±7 mg/kg/day; dose adjustment was based on iron intake and on liver and cardiac iron overload at CMR. Despite different durations of deferasirox exposure and different levels of myocardial iron overload, an average improvement of myocardial T2* from 27.4 ms to 29.8 ms was observed at T1 (P=0.004). A significant improvement in LVEF from 63.6 % to 66.5 % (P=0.013), indicative of improved cardiac function, was also observed. Similarly, both end-systolic and end-diastolic ventricular volume assessments (EDV, EDVI, ESV, ESVI) showed significant improvement at T1. No difference in median serum ferritin levels were found between group A and B. Myocardial T2* increased in both groups with DFX treatment, with a significant improvement observed in Group B patients (T2* at T0 was 15.7 ± 2.7 ms and at T1 19.6 ± 3.8 ms, P=0.003) (Table 1). LVEF significantly increased in both groups, from 65.7% to 68.0 % in Group A (P=0.01) and from 59.7% to 64.3% in Group B (P=0.04) (Table 1). In Group A, improvements in EDV, ESV and ESVI were also significant with deferasirox treatment; in Group B significant improvements were observed in ESV and ESVI (Table 1). CONCLUSION. These data confirm the effects of iron chelation with deferasirox in removing cardiac iron in beta TM patients with mild-to-moderate myocardial iron overload and preventing accumulation of myocardial iron in patients with normal baseline cardiac iron levels. Interestingly, improvements in cardiac function were observed both in patients with and without myocardial iron overload at baseline, however it was more significant in patients with normal T2* at baseline. Disclosures: No relevant conflicts of interest to declare.

Iron Chelation Therapy in CAPD: A New and Effective Treatment of Iron Overload Disease in Esrd Patients

1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz
Keyword(s):  
Peritoneal Dialysis ◽  
Iron Overload ◽  
End Stage Renal Disease ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Peritoneal Dialysate ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.

STUDY OF GHRELIN LEVELS IN HYPOTHYROID PATIENTS BEFORE AND AFTER TREATMENT

2021 ◽  
pp. 52-54
Author(s):  
Peeyush Yadav ◽  
G. G. Kaushik
Keyword(s):  
Treatment Group ◽  
Thyroid Hormones ◽  
Hdl Cholesterol ◽  
Metabolic Disturbances ◽  
Free T4 ◽  
Before And After ◽  
Group A ◽  
Group B ◽  
Serum Ghrelin ◽  
Hypothyroid Patients

Objective: Aim of the present study was to evaluate the levels of ghrelin in hypothyroid patients before and after treatment with L-thyroxine and to nd a possible relationship between ghrelin and thyroid hormones. Material & Methods: The present study was conducted on 100 hypothyroid patients (44 Males & 56 Females) before treatment (Group A) and after treatment (Group B) attending the outpatient clinics or admitted in wards of J.L.N. Hospitals, Ajmer. 100 healthy control subjects (Group C) of same age group of either gender were selected for the study. Blood samples were drawn from patients and controls, after overnight fast of at least 8 hours. Estimation of Serum Ghrelin, free T3, free T4, and TSH was done by using Enzyme- Linked Immunosorbant Assay (ELISA) technique. Total Cholesterol, Triglyceride, HDL – Cholesterol were measured by automated analyser (Beckman & Coulter's AU680). VLDL – Cholesterol, LDL – Cholesterol were calculated by Friedwald's formula. Differences in the parameters among the groups were analyzed by ANOVA test followed by its Tukey HSD post hoc analysis. Correlations between variables were tested using the Pearson rho (r: Correlation coefcient) correlation test. Results: Findings of the present study shows that the levels of serum fT3 (1.79 ± 0.29 pg/mL) and serum fT4 (0.34 ± 0.11 ng/dL) were signicantly lower in Group A compared to Group B (fT3 = 3.00 ± 0.32 pg/mL & fT4 = 0.81 ± 0.15 ng/dL) and Group C (fT3 = 3.12 ± 0.31 pg/mL & fT4 = 0.85 ± 0.11ng/dL) whereas serum TSH levels were signicantly higher in Group A (40.59 ± 13.55 μIU/mL) compared to Group B (5.34 ± 1.47 μIU/mL) and Group C (3.23 ± 1.04 μIU/mL). Levels of serum Ghrelin were signicantly higher in Group A (918.19 ± 48.47 pg/mL) compared to Group B (700.34 ± 46.35 pg/mL) and Group C (681.49 ± 35.80 pg/mL). A non signicant correlation of Ghrelin with S.fT4 and TSH was found in both Group A and Group B whereas S.fT3 and BMI shows a non signicant correlation in Group A in comparison to a signicant correlation in Group B. Conclusion: There is a reversible increase in the levels of serum ghrelin which became normalized after L-thyroxine substitution in hypothyroid patients. Alteration in the levels of serum ghrelin in thyroid disorders indicates a compensatory role of ghrelin in metabolic disturbances and also suggests a possible association between thyroid hormones and serum ghrelin levels.

scholarly journals Endocrine complications

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Membrane Lipids ◽  
Survival Rates ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Cellular Iron ◽  
Active Iron ◽  
Bone Changes ◽  
Endocrine Complications

More than five decades ago, thalassemia major (TM) was fatal in the first decade of life. This poor prognosis changed since the survival rates started to increase progressively thanks to the implementation of continuous and significant improvement of diagnostic and therapeutic methods, consisting mainly of an intensive transfusion program combined with chelation therapy and imaging methods. Regular red blood cell (RBC) transfusions eliminate the complications of anemia, compensatory bone marrow expansion, bone changes and splenomegaly, restore the physiological growth throughout childhood and extend survival. The most serious disadvantage of life-saving transfusions is the inexorable accumulation of iron within tissues. Iron is physiologically stored intracellularly in the form of ferritin, a protein whose synthesis is induced upon the influx of iron. When the storage capacity of ferritin is exceeded, pathological quantities of metabolically active iron are released intracellularly in the form of hemosiderin and free iron within an expanded labile pool. This metabolically active iron catalyzes the formation of free radicals, which damage membrane lipids and other macromolecules, leading to cell death and eventually organ failure. Other factors contributing to the variability of cellular iron overload are: a) the cell surface transferrin receptors and the capacity of the cells to deploy defence mechanisms against inorganic iron; b) individual susceptibility to iron toxic effect; c) the development of organ(s) damage secondary to persisting severe iron overload in the years preceding iron chelation therapy; and d) liver disorders, chronic hypoxia and associated endocrine complications. Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists.

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